PXD066371-1

PXD066371 is an original dataset announced via ProteomeXchange.

Title	Ketone Bodies-mediated Cysteine Modifications Discovered by Chemical Proteomics
Description	All the studies of ketone body-dependent post-translational modifications (PTMs), notably those mediated by ketone bodies, β-hydroxybutyrate (Bhb) and acetoacetate (Acac), have focused on lysine acylations. However, given the chemically diverse and reactive nature of metabolites generated, it remains unclear whether non-lysine modifications can also happen. Here, we report the synthesis of an acetoacetate-alkyne (Acac-alkyne) chemical probe that enables efficient metabolic labeling, robust fluorescent visualization, and mass spectrometry-based identification of Acac-modified proteins. By combining chemical proteomics with open-search strategy, we showed that Acac will induce previously uncharacterized cysteine modifications in mammalian cells. Notably, cysteine S-crotonation (Ccr) is validated by employing both probe-based and standard peptide-based co-elution assays. Metabolic pathway tracing further identifies BDH1 and ECHS1 as key enzymes that generate Ccr formation. Together, these findings establish ketone metabolism as a novel source of cysteine modifications and provide an alternative mechanistic pathway to explain the profound biological effects of ketone body.
HostingRepository	iProX
AnnounceDate	2025-07-22
AnnouncementXML	Submission_2025-07-21_20:16:38.694.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuanfei Zhou
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 240; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-21 20:16:17	ID requested
⏵ 1	2025-07-21 20:16:39	announced

Dataset with its publication pending

submitter keyword: Ketone Bodies, Cysteine Modifications, Chemical Proteomics

Zhipeng Wang
contact affiliation	Desai Sethi Urology Institute & Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
contact email	zaw29@miami.edu
lab head
Yuanfei Zhou
contact affiliation	Desai Sethi Urology Institute & Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
contact email	yxz2215@miami.edu
dataset submitter

iProX dataset URI